Fasting For Longevity: Valter Longo, PhD Shares Cutting-Edge Fasting Science & Optimal Nutrition Protocols For Lifespan Extension & Disease Prevention

Dr. Valter Longo is a pioneering longevity researcher, Director of the USC Longevity Institute, and one of TIME’s 50 most influential people in healthcare. This conversation explores his groundbreaking Fasting Mimicking Diet and its profound implications for aging, disease treatment, and longevity. From cancer therapy to diabetes reversal, Valter reveals how therapeutic fasting could transform modern medicine. Along the way, Valter challenges my long-held assumptions about protein intake and sleep. His research offers hope for extending human healthspan, and this conversation is illuminating at every turn. Enjoy! Show notes + MORE Watch on YouTube Newsletter Sign-Up Today’s Sponsors: Seed: Use code RICHROLL25 to get 25% off your first month 👉https://bit.ly/seedxrrp2025 Squarespace: Use code RichRoll to save 10% off 👉https://bit.ly/squarespace2025 Go Brewing: Use the code Rich Roll for 15% OFF 👉gobrewing.com iFit: Use the code RICHROLL to get 10% off any purchase of $999+ 👉 nordictrack.com/RICHROLL LMNT: Get a FREE LMNT sample pack for just $5 shipping 👉 drinkLMNT.com/RICHROLL BetterHelp: Use the code RICHROLL to get 10% off your first month 👉BetterHelp.com/richroll Check out all of the amazing discounts from our Sponsors 👉 richroll.com/sponsors Find out more about Voicing Change Media at voicingchange.media and follow us @voicingchange Learn more about your ad choices. Visit podcastchoices.com/adchoices

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Rich Roll?

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• 1:06Valter Longo?

  It's a very undisciplined world. If you look at Europe, 60% of people are overweight or obese, and in the United States it's 75%. If you can make somebody younger, they will live longer, they will be much healthier. Of course, you cannot make somebody live 10 times longer, but could you make him 50% longer, right? So I think it's possible, right? So from 80 to 120.

• 1:28Rich Roll?

  Returning for his third appearance on the podcast, I'm very pleased to welcome back Dr. Valter Longo, a pioneering research scientist in the field of longevity, fasting, and age-related disease. Named one of the 50 most influential people in healthcare by Time Magazine, Dr. Longo is both the director of the Longevity Institute at USC, where he is also a professor of gerontology and biological sciences, as well as the director of the Longevity and Cancer Program at the Institute of Molecular Oncology in Milan, Italy.

• 2:01Valter Longo?

  Fasting mimicking diet plus chemo, immunotherapy, hormone therapy, kinase inhibitor. I mean, the potential is huge. All the different cancers and in all the different stages.

• 2:14Rich Roll?

  In this conversation, we parse longevity science from myths. We talk about the most important habits to consider to keep aging and disease at bay, the optimal way to fast, and what Dr. Longo's research reveals about the impact of fasting on our biological clock, on lifestyle disease generally, and on the prevention and treatment of various types of cancer, which is also the subject of his latest book, Fasting Cancer. Dr. Longo is truly at the cutting edge of a field that is rapidly rewriting the rules on how to live longer and more vitally. It's incredible stuff, and my hope is that this conversation will leave you rethinking your non-ideal nutrition habits and empowered to make better ones.

• 2:58Valter Longo?

  What you eat every day is going to have a huge impact on your health span and lifespan. What is it about these diets that is so protective?

• 3:11Rich Roll?

  Valter, thank you for returning to the podcast. It's been between like two and a half and three years since we last sat down to talk. We reconnected at that Google conference recently where you were on a panel with Rhonda Patrick and Peter Diamandis, who both have been on the podcast recently. So you're completing the triumvirate here to kind of dive deep into longevity science, fasting. We're going to talk about the impact of the fasting mimicking diet on cancer specifically, which is the subject of your new book, Fasting Cancer. But before we get into all of this, I think it would be valuable to just spend a minute or two discussing what has transpired in the last 24 hours.

• 3:56Rich Roll?

  So today is January 23rd when we're recording this. We're on day four of the Trump administration. And just yesterday, there was a freeze on NIH grant review panels. There was an article in science.org about this. So there's a little bit of a mild panic among scientists who depend upon grant funding, whose studies are under the umbrella of the NIH, which is an enormous institution. I think something like 300,000 people, 2,500 institutions underneath that.

• 4:31Rich Roll?

  And it perhaps is a momentary pause. Certainly, I would imagine there's bloat in this bureaucracy that is worthy of review, but at the same time, interruption in billions of dollars in research funding. So as a scientist who runs a lab, I suspect you are potentially impacted by this and just wanted to see where you stand and what your thoughts are on this.

• 4:54Valter Longo?

  Yeah, well, we're very worried, of course. I just submitted a grant to the NIH, and this is a $15 million grant. It's a major grant for my lab at USC, and we depend on that, right? So we depend on these NIH funds to do research. My group has helped maybe 50 universities and hospitals do clinical trials. Without the NIH research, none of those would have happened. And our trials, I think, are particularly relevant because they're not on drugs. So there are trials on fasting, fasting mimicking diets and longevity diets. So things that are either free or inexpensive, and those, particularly those, depend almost

• 5:37Valter Longo?

  completely on the NIH and sometimes on some foundation funding, but mostly on the NIH. So obviously, there's reform needed at the NIH, and I think most of the NIH people will say the same, right? Certainly, blocking the NIH process is a big problem.

• 5:55Rich Roll?

  Yeah, I think they are responsible for something like $47 billion in allocations. And I think it's kind of important to understand that not all research is pharma-funded and foundations only go so far, right? Like, in terms of how we underwrite critical research, not just in terms of clinical trials, but all manner of research to find new cures to diseases, et cetera, it goes well beyond kind of what I think perhaps people might imagine in terms of its scope and depth.

• 6:29Valter Longo?

  Yes, and I think a lot of people maybe think that this is just about basic science, but in fact, the NIH funds a lot of clinical trials, and some of these clinical trials could have an almost final impact on whether an intervention gets used or not by people eventually, right? So in some cases, they may even fund trials that are going to be FDA-approved. So, yes, so it's basic research that fuels the translational science. Or transitional science and then transitional science that fuels clinical trials and treatments. And I think that with that NIH would be a drastic problem,

• 7:08Valter Longo?

  especially for those diseases or problems where the big pharma don't want to invest, right? So like rare diseases and diseases that are not that profitable. So that's where the NIH steps in and funds the research and clinical work to treat it.

• 7:30Rich Roll?

  Yeah. Well, interesting times indeed in which we live. But we were both lucky enough to avoid our homes being impacted by the recent fires, although there's fires still burning right now. So it's a very, you know, it's a very interesting time here in Los Angeles. Anyway, because it's been a couple of years since you've been here, I thought it would be great to kind of catch us up on the latest findings with respect to fasting, the fasting mimicking diet, which is your kind of like focus, intermittent fasting, time restricted eating. There's a lot of confusion out here around that. Last time you were on, we kind of canvassed all of these, but a lot has happened in the intervening kind of period in which we last sat down.

• 8:12Rich Roll?

  So kind of where are we and what's got you kind of excited or what's giving us greater clarity about the impact of this science?

• 8:20Valter Longo?

  Yeah, so I would say that, at least in my opinion now, the more clear evidence for fasting is in the time restricted eating domain, you know, so that the daily fasting. And I think we discussed it before, but I stick with the 12 hours of fasting and 12 hours of feeding per day. And there's new data indicating that, in fact, maybe the problem of skipping breakfast and doing 16 hours of fasting and skipping breakfast may not be about skipping breakfast, but maybe about the 16 hours, right? So we don't know, but certainly that's a possibility. And so I think 12 hours is a much safer way to go.

• 9:03Valter Longo?

  And that is effective, of course, is 16 hours of fasting every day. But still effective. And so I think Satish Impala and I will agree on the say 11 to 12 hours daily, time-restricted period. So eat for 11 hours or 12 and fast for 13 hours or 12.

• 9:24Rich Roll?

  My understanding, correct me if I'm wrong, is that we still need more research to really drill down on the efficacy of these specific windows. But as of right now, it's sort of a safe bet. Like this 12 on, 12 off seems to be the one that kind of works for all purposes, whereas others may have benefits or deleterious impacts that we're still trying to better understand. But as of right now, this seems to be the window that is the safest and most predictable in terms of outcomes.

• 9:58Valter Longo?

  Yeah, the easiest, safest. No physician will ever argue that that's a bad idea. And really not a single paper saying that this is not safe or that is not effective or at least partially effective in preventing and treating a number of diseases. So yeah, so I think it's a good compromise and I think it's something that everybody should do. And it's also consistent, not just with the epidemiological data, the clinical trials, also consistent with what centenarians have been doing for 100 years or more. So yeah, so I think that 12 hours is one.

• 10:40Valter Longo?

  And then I've always argued against the alternate day fasting, the 5-2, not because they're not effective, but again, they're very demanding, right? So not eating every other day, it's going to be something that very few people will ever be able to do. And then you get into, again, the territory of are there side effects caused by not eating every other day or not eating for two days a week? So I would say in general, I just don't see a big future, at least not for the general population, right? Some people can do it. We'll see about the efficacy and the safety.

• 11:20Valter Longo?

  But I think that in general, I would say that at least I'm not enthusiastic about either alternative fasting or two days a week of fasting. Then, of course, I'm enthusiastic about the fasting mimicking diet. So in addition to the time restricted eating daily, then the cycles of the fasting mimicking diet. And so this is a plant-based, you know, low calorie, low sugar, low protein, high plant-based fats. The program that we've been testing, we and many universities have asked to test it, have been using it for all kinds of diseases, from diabetes, prediabetes, cancer, Alzheimer's,

• 12:03Valter Longo?

  autoimmunities, et cetera, et cetera.

• 12:06Rich Roll?

  For people that didn't listen to our previous episode, the fasting mimicking diet is essentially a way of eating a calorie restricted diet with a very specific, you know, kind of menu that physiologically mimics what the body would experience had it been just fasting, correct? Is that, do I say that accurately?

• 12:28Valter Longo?

  Yeah, that's accurate. So then that was first developed in mice. And so we use certain markers to make sure that there is a fasting response equivalent to that of water-only fasting. And then the same was done in people. And again, we're looking for certain factors in the, in the blood that would show that in fact that that person has responded as it would if it was not eating at all.

• 12:53Rich Roll?

  Before we move on from time restricted eating in this 12-hour window, you know, to restrict your eating to a 12-hour period isn't really fasting at all. It's sort of like if you get up at eight in the morning and you go to bed at nine or 10 at night, like there's literally only an hour or two in which you're not meant to be eating.

• 13:12Valter Longo?

  Right, yeah, and that's very important, right? Because if you look at Europe, 60% of people are overweight or obese, and the United States is 75%. So we're in a world, I think, and this is not just Europe and the US, it's the whole world with few exceptions. So it's a very undisciplined world. And so that's very important to also say, not just what will be most effective, but what will be easiest for people, realistic for people. And so I think that 12 hours, a lot of people say, "That's not fasting at all." Well, it is fasting, because now, on average, and this is work by Panda, people were eating for about 15 hours a day. So, yeah, so people all over the world like to eat for long periods every day.

• 13:56Valter Longo?

  Yeah, so then somebody may start at 6:00 a.m. and end at 11:30 p.m. Right. And so that, you know, the three, four, five-hour restriction can make a big difference. It can make a big difference, not just in reducing calories, because you have less opportunities, but also in metabolic switches that may make energy expenditure higher, let's say, right? And also help people sleep. So those are some of the things that are emerging in mouse and human studies.

• 14:27Rich Roll?

  If people are eating on average 15 hours a day, is there evidence, or is anybody kind of looking at the co-founding factor of the impingement on sleep that would be impacting deleterious health outcomes? Because if you're eating for that many hours, you're probably staying up late and not getting, you know, this, the eight hours that you should be getting, or seven hours?

• 14:48Valter Longo?

  Yeah, so Sachin Panda published on that and showed that, in fact, when they reduced the eating window from 14 hours and above, if I remember correctly, to less than 11 hours, there was an improvement in sleeping quality. So, yes, so that seems to be the case. And I've always been also preaching not eating for the last three hours before you go to sleep.

• 15:12Rich Roll?

  Yeah.

• 15:13Valter Longo?

  So that's consistent.

• 15:14Rich Roll?

  That's still the hardest thing for me. It's really, it's really difficult for me to go to sleep when I don't have a full stomach or, or I'm feeling hungry at night. It's just a mountain I still have not mastered.

• 15:27Valter Longo?

  Yeah, and I think it's important, you know, the foundation clinics, we, everybody's got a different method, right? So, so I think it's important. So, for example, it's better to eat a light dinner, but I have a very big dinner, right? So, because I'll be unhappy having a big lunch and a small dinner. So, so to me, it works. For me, it works. And so I think it's okay. I sleep well and, or pretty well, unless I'm traveling like I, like I just did. But yeah, if you, if you eat late, then, and that's a big deal to someone. But that doesn't really affect you negatively. I don't think there is too much

• 16:08Valter Longo?

  data suggesting that you're gonna live 10 years shorter because of that, right? So, so if you're sleeping well, that's probably okay. And okay, compromise.

• 16:16Rich Roll?

  I do notice, though, if I overdo it in terms of volume and, you know, hour of the evening, I'll generally wake up around two or three in the morning. And when I was wearing a CGM, I would notice, you know, these spikes and these drops that would occur, you know, over the course of, of the evening that don't happen when I eat earlier or like reduce the volume.

• 16:36Valter Longo?

  Right. And as you get older, they might get worse, right? So, so, yeah. So then, yes, the recommendation stays eat earlier and eat within 12 hours. And then, you know, if somebody is not affected by, by eating later, it's probably okay until that becomes a problem, right? So I think that's a good way to look at it. And of course, you have to know that it's a problem, but you know, not sleeping well, most people will know even without a bracelet.

• 17:06Rich Roll?

  You'll know, yeah. You don't need any, any kind of like data feedback to know whether you're sleeping well or not, honestly. Before we kind of even go further, perhaps we should just take a minute and, and, you know, set the table a little bit. Your expertise is on nutrition and its impact on longevity and disease prevention and to some degree disease treatment through the lens of fasting. So maybe, you know, in your own words, kind of describe, you know, your research and kind of the thesis of the work that you do.

• 17:42Valter Longo?

  Yes, so that's, let's say, fifty percent of what we do is what you just described, so the fasting making diet. And the origin of that is in something called calorie restriction, which we talked about in the past. And the fact that, you know, my former mentor was, you know, one of the pioneers of calorie restriction, which is just, you know, what happens in a normal person that has a normal diet if you reduce the calories by twenty, twenty-five percent. And my observation that that was just not feasible and not very difficult for people to do and potentially giving problems and solutions, right? So then the fasting making diet was about, can we get the same effects as this phenomenal

• 18:25Valter Longo?

  effects that calorie restriction has been demonstrated to have in monkeys and lots of different animals and in people without the problems, right? So that was the idea, like, maybe you do this five days once a month and maybe you do it as little as every three or four months. And that's what we're actually testing now in southern Italy on a big cohort. Yeah, so the fasting making diet is that and we can talk about it. Then we're working on what I call the longevity diet, and that's a big part. And so, in fact, we have a number of papers that are going to be published in the next year or two, which is about what if you eat a normal diet, you know? So we've been talking about Mediterranean diet and ketogenic diet. And so we just tested them all, right?

• 19:07Valter Longo?

  So in mice, and now we're testing a lot of these diets and we're comparing them, you know? So what if you can compare a vegan diet and a ketogenic diet and what I call the longevity diet, which is a pescatarian diet? How do these affect aging, longevity, age-related diseases, and also frailty and strength, right? So that's another big part of my laboratory. What do you eat every day? So let's move away from words like Mediterranean diet or Okinawa diet and just move into what is it about these diets that is so protective? Is it the protein? Is it the type of protein, right? So, for example... You could say high protein, low protein, and I will argue it's irrelevant, right? Because you can have a five to tenfold difference

• 19:52Valter Longo?

  in certain amino acids with the same level of proteins. You know, if you eat legumes versus you eat... And sometimes you can have that between different plant-based sources, right? You can have a five-fold difference of, I mean, certain essential amino acids between two different plant-based sources. So I think we probably need to move away from also same protein in levels, right? And move into amino acid profiles. Anyways, it's just, I think the pillar number two of my work is, you know, what you eat every day is going to have a huge impact on your health span and lifespan. And so what is it that you should change among all the things that you eat? And how do you personalize it, right? Because I always say, you know,

• 20:37Valter Longo?

  you can have eggplants and be very healthy, or you can have eggplants and be miserable because they happen to cause an inflammatory response in you, right? So, yeah, two people, you know, maybe even brothers and sisters, right? One could be having eggplant all day and one could be very much sensitive to it. So, yeah, so then the everyday, I think diet is another important thing. And the third one is genetics, right? So not just, we don't look at diet in a vacuum. We look at diet, whether it's fasting or eating, as how does it affect the genes that regulate the aging process? How does it affect IGF-1, growth hormone, growth hormone receptor?

• 21:21Valter Longo?

  How does it affect TOR, you know, RAS? And all these genes, these networks that are now clearly, and we talked about in the past, a simple organism, we can manipulate these genes. And if we combine fasting with genetic mutation, we make simple organism live 10 times longer, right? So we're trying to bring that to people. So, you know, of course, you can make somebody live 10 times longer, but could you make him 50% longer, right? So I think it's possible, right? So from 80 to 120, that is possible. And, yeah, and I think all of this has to be understood very well and put together in a way that will cause the benefits without the problems, or without generating new problems.

• 22:07Rich Roll?

  It's so complicated. You know, there are general principles and yet there are, you know, there's diversity to your point about the eggplant that you have to address. And I think what's interesting about your work is that, and maybe what's somewhat unusual about you as somebody who is a research scientist, is that you are thinking about how you balance your discoveries around efficaciousness with sustainability and adherence in the general population. It's one thing to look under a microscope, have a discovery and extrapolate from that into some sort of principle, but you know, how can that be translated into something that the average person can take and use, sustain, that will benefit them over time?

• 22:51Valter Longo?

  Yes, and I think that we want to take it all the way to disease cures, not just treatment, cures, right? So now, for example, with diabetes, we now have three or four trials, all of them showing a 50 to 70% regression of the disease and then-

• 23:12Rich Roll?

  On the FMD?

• 23:13Valter Longo?

  On the FMD, just once a month without changing their diet. And that's a very important thing, right? So we don't change their diet, we don't change their lifestyle. And we're saying, so you know, for thousands of years, people have been talking about food as medicine, right? But it really never happened, right? So that's what we're trying to do, say, can we standardize this, you know, vegan-based medicine and then use it to, in some cases, even cure diseases? And so diabetes, I think, is definitely one of the ones where we're very confident. And so University of Leiden, or the University of Heidelberg did the first trial a couple of years ago and showed impressive, impressive effects on A1C, but also on reduction of drug use.

• 23:56Valter Longo?

  And then Leiden repeated and got the same results. And so I think, yes, this is feasible ways to bring people back to a functional state, from a disease state to a functional state. And I think that, you know, a lot of that has to do with molecular mechanisms that are much more sophisticated than people, you know, may imagine. So, for example, we just published in collaboration with Laura Perrin at a children's hospital, we published on the use of the FMD in kidney, in rats with kidney damage, and then in people with kidney disease, right? But in people, of course, we don't get to see what happens, but in rats, we get to

• 24:40Valter Longo?

  see what happens, and it's really remarkable. So we damaged the kidney, and you see a complete disruption of the gene expression. So our genes are turned on and off in the different cells of the kidney. And then we start the fasting mimicking diet, and you see that, so there is a very precise architecture, let's say, right, three dimensional, and then they're completely destroyed by this toxin that we give the rats, right? Then we start the fasting mimicking diet cycles, and you see everything going back to where it was, right? Almost like a magic intervention. So it's not really the fasting mimicking diet that is doing anything, right? It is the rat that always, and people are the same, that always had programs that are

• 25:25Valter Longo?

  able to be triggered by fasting, to turn on regenerative and developmental-like programs. So the same genes that are used when the organ, when the kidneys are first generated in a baby.

• 25:42Rich Roll?

  Like pluripotent stem cell generation? Is that what you're talking about?

• 25:46Valter Longo?

  Yes, yes. So the cells are being reprogrammed into some of these reprogramming factors, the yamanaka factors, also known as yamanaka factors, are turned on. And you see that every organ is turning on different ones, right? So in some cases, you see OCT4 being turned on, in some cases, you see MYC. So different organs use different ones, but they all have the same thing in common. They turn on these many genes that are involved in cellular, in organ generation, and then that's how they can go from this very disrupted state back to the previous healthy state. So they know exactly, you know, what to turn on to get back, to fix the problem.

• 26:30Valter Longo?

  So yeah, so then that's the power of this fasting making diets. So turning on the ability of the body to fix itself. And so now, you know, diabetes, we're seeing it, we're seeing now with kidney disease. We are now seeing it with, I mean, at least this is in humans and animals. But for some other like gut, we are clearly seeing it in animal studies. And now there are many, a number of trials that will test it in clinical trials.

• 27:03Rich Roll?

  What is your understanding of the, you know, kind of mechanistic landscape here? How much of this can be attributed simply to caloric restriction? How much to the timing window? And how much to the, you know, kind of macro composition of the FMD or whatever kind of fasting diet that one is on?

• 27:25Valter Longo?

  The eating window, none, because we don't use eating window in the FMD diet. So people can eat for 18 hours a day if they want to, right? So that's in that case, I'm not saying that that's not beneficial, as we discussed earlier. But not in this case. Calorie restriction, probably none, because per month, mice rats and probably people, they eat about the same amount. So they overeat anything they didn't eat during the FMD five days, right? So they have 25, 26 days to even overeat a little bit. And this is what we see very clearly in animal models that per month, rats that receive the fasting making diet eat the same level of calories

• 28:09Valter Longo?

  as the control, as those under control diet. Yeah, so I think it's mostly signaling, some of it seems to be stem cell activation. So for example, in the blood, we see an increase in what's called LTHSCs, hematopoietic stem cells. So in the blood, it seems to be stem cell driven. In lots of other organs, the gut, the kidney, and some other tissues, it seems to be reprogramming, right, which we just discussed. So I think that on one side is this stem cell reprogramming mechanisms. And on the other side, it's probably metabolic, metabolic switches. What does that mean? It means that

• 28:55Valter Longo?

  People and all kinds of organisms, they can be in a fat storing mode, or energy storing mode, or in an energy burning mode. So if it's summer and you have plenty of food, you have excess food, you wanna put it away, right? And if it's winter and you don't have any food or food that is scarce, then you will start using those reserves. That's the other big effect of the fasting making diet is unlocking that. But very importantly, and I don't remember if we talked about it before, without getting the organism into a thrifty mode, right? So because if you go long enough, now we know from calorie restriction studies and lots of, lots of human studies,

• 29:39Valter Longo?

  that eventually if you starve or restrict the system of a human body for long enough, it'll go into an energy saving mode. And so you wanna trigger this metabolic switch from the fat storage to the fat burning, but don't get into the thrifty mode, which now is gonna try to save anything that it can. So lower energy expenditure and save it because the system is worried about running out of fuel. So it's very tricky, right? And this is why the five days of the fasting making diet, and then go back. Because, and that's why also eating is probably important, right? So you're eating, but you're restricting for five days.

• 30:21Valter Longo?

  And the message is, okay, get out of the energy saving mode, burn the fat, and we see the ketone bodies go up and, you know, and the fat burning clearly going up. But don't enter this energy saving mode. Because we're okay, we're not gonna starve.

• 30:40Rich Roll?

  Right, so from a layperson's perspective, that would mean an emergency state in which the body is essentially saying like, slow the metabolism down, like we gotta conserve everything because, you know, we don't know when we're gonna get our next meal and everything kind of goes into low power mode.

• 30:56Valter Longo?

  Yes, and that low power mode could last years, right? This is why sometimes you hear people saying, I don't know what happened, I'm not eating anything, and I cannot lose weight, right? And this, this is a big problem, right? And this is what people understand, the devil is in the detail. If you get into that, it could be epigenetically regulated. What does it mean? It means that the DNA can get modified to impose this thrifty mode, right? Impose that. Energy expenditure should be the lowest, as low as possible, because that's my biggest problem, that you're going to starve to that. And so for a couple of years, I'll keep you in this energy-saving mode, and then we'll see, if things are consistently better, maybe I'll get you out of it, right? So, yeah, so I think that a lot of that is happening,

• 31:41Valter Longo?

  and very few clinics that are dealing with people that are overweight and obese, understand this. And so without this understanding and intervening, it's very difficult to get the person out of this potentially epigenetic lack that makes them just hungry all the time, and with low energy expenditure, so making it impossible.

• 32:04Rich Roll?

  Yeah, I think that's a sort of common but under-discussed thing that happens with people who are sort of chronically overweight, and they've gone on a lot of extreme diets over the years, and restricted their eating, et cetera, and are in that state where now, they'll say, like, it doesn't matter what I do, I can't lose weight, it doesn't matter how much I exercise, and I'm doing all the right things, and I'm kind of in this place where I just, you know, maintain the same overweight status forever, my energy levels are low, et cetera, all of that. So for somebody who is experiencing that, or is listening to this and is relating to that, what is that long road out of that? Like, how do they, you know, where should they kind of direct their attention to claw out of that hole?

• 32:48Valter Longo?

  Yeah, so, I mean, so the Creative Heroes Foundation that I started has dieticians that are specialized in this. It's a nonprofit, it's here in Los Angeles, but they can follow anybody, anywhere. We usually apply four things. We apply the longevity diet, it's pescatarian, low protein, mostly plant-based diet, the fasting-making diet, and the 12-hour time rest of the evening, and then the exercise, right? And this, a combination of this, and some people say, "I don't want to do the fasting-making diet." And so people say, "I don't want to do the longevity diet." But, you know, most people say, "Okay, I can do three out of four, or two out of four." I would say that it takes about one to two years to get.

• 33:32Valter Longo?

  Somebody back to where they need to be and just comfortable with with this new diet. And a lot of times we try to minimize the changes, right? We really focus on not giving you, here's a diet that you should have. It's more, what is your diet? And what are the problems that you're having? Can we change this? And can we minimize the changes that you have? As long as you think you can keep them for the rest of your life, right? So that's really the important thing because, and I'm sure we discussed it before. If you start doing this yo-yo, then you're in trouble, right? And then it's worse than having done anything at all, right? So it's better to just keep the weight and keep the problems rather than losing and regaining.

• 34:17Valter Longo?

  And that's what the great majority of people do.

• 34:34Rich Roll?

  It's one thing to talk about fasting in the context of weight loss. I mean, let's be honest, that's probably what gets most people interested in this world to begin with. Another thing to talk about it in the context of chronic lifestyle disease prevention. But certainly, you know, if it helps you to lose weight, then you're at a lower risk for, you know, kind of being afflicted by many of those diseases. And then another thing altogether to talk about disease reversal, which you already sort of touched on. What was the lightning bolt moment for you where you began to see like, oh my Lord, like this actually has an impact on reversing conditions that people have, like serious conditions?

• 35:15Valter Longo?

  Well, of course, we've been working on cancer for a long time. But as far as multi-system regeneration, I think the first one was our work on chemotherapy and the immune system, right? And the blood and immune system. So, you know, the mice would get chemotherapy and there would be dramatic or drastic negative effects, of course, on the immune system and the white blood cells. And they will come down and stay down. And this is a problem that a lot of cancer patients have, right? It's all. Then we started doing the fasting making that cycle or the fasting cycle. Back then, we were not, it was more than 10 years ago. We're not even working with the FMD. We were working with just water only fasting in mice.

• 35:57Valter Longo?

  And we saw that the stem cell, we saw the white blood cells, so the immune cells would come back up only in the mice that were given chemotherapy plus fasting cycles, right? And so we said, is it possible? They come down. So the fasting was not protecting the lowering of the white blood cells. It was just making them come back up to normal within a couple of months, right? And so it turned out to be, it was stem cells, right? So the FMD cycles were turning on the bone marrow stem cells.

• 36:30Rich Roll?

  Right.

• 36:30Valter Longo?

  And the bone marrow stem cells, it took a couple of months to regenerate healthy white blood cells and repopulate the normal immune system, right? So really remarkable effect. And then we had a follow up paper with the pancreas where we, you know, completely damaged the pancreas in animals. So completely blocked insulin production by the pancreas permanently. And then we started the FMD cycles. And then you see that, again, this two Yamanaka factors being turned on in the pancreatic cells, in the beta cells of the pancreas. And then after, you know, a couple of weeks, insulin will get back to normal.

• 37:08Valter Longo?

  And so this was, you know, showing that the pancreas can fix itself and can go back to normal insulin production, you know, so essentially treating type 1 diabetes, right? And so those are the two papers that I think, one stem cells and the other one reprogramming in a very sophisticated way, right? So I'm always entertained by, you know, the sort of pharmaceutical point of view that, you know, drugs are sophisticated and what could nutrition possibly do, right? And instead, I think you see evidence for, you know, nutrition starting something that is so sophisticated and it's so old, right?

• 37:50Valter Longo?

  It's billions of years old and has been, has evolved for the process of, for the purpose of fixing lots of things in a way that. It would be unimaginable with any cocktail or drugs or intervention that you could think of for now, right? Maybe 20, 30 years from now, we'll have artificial intelligence-driven repair systems and it'll be another world. But I think that it's going to be hard for a while to beat that extremely sophisticated, you know, three billion-year-old system that has the job of identifying a problem and, you know, coming up with a solution.

• 38:32Rich Roll?

  Yeah, it's been designed through evolution over so many years to, you know, work in a way that the blunt instrumentation of pharmaceuticals can't. Like, they're directed at one thing very bluntly, and then there's all sorts of downstream implications and side effects from that that you don't see with the nutrition intervention, right?

• 38:53Valter Longo?

  Well, you can see it with the nutrition intervention if you misapply, right? If you don't understand mechanisms, you could cause problems, right? It's very powerful. And so if you don't understand how it works, then you could do a lot of damage. I'll give you an example. There was a paper recently. So for the longest time, we've been saying, if you give chemotherapy to a mouse or a person, don't refeed the mouse or the person while the chemotherapy is still high in the system, right? Because the refeeding means the growth factors go way up, and now you have a very quick proliferation of cells while there's a lot of chemotherapy in the system, right? And so a year ago, somebody published an intermittent fasting, like, I think it was

• 39:35Valter Longo?

  alternate-day fasting, showing that the opposite of what we have shown for long-term fasting by using, you know, everyday fasting. So they give chemotherapy, and then they cycled normal food fasting, normal food fasting. So now you have high levels of chemotherapy together with the refeeding. It's a very bad combination, right? And as we had predicted, the cardiotoxicity went up instead of down, right? So the, you know, two different methods of fasting, one causes, you know, really remarkable protection of the heart, the other one causes remarkable damage to the heart. And both of them are called fasting. This is why it's very important to, you know, standardize it, make food as medicine, test it very carefully, understand the mechanism,

• 40:20Valter Longo?

  and then, you know, and then and only then it would beat, I think, lots of drug-based approaches.

• 40:27Rich Roll?

  Yeah. Some of the remarkable study results come from rats and mice. You talked about the kidney and the pancreas, et cetera. How much of that can we sort of extrapolate to apply to humans? Obviously, you can't study humans in the same way. Like, I'm always confused about, you know, how, how much we can read into these animal studies in terms of their applicability to human biology.

• 40:50Valter Longo?

  I think that, I mean, of course, so we, we're running trials, right? We, we, but we, I mean, lots of universities, and a lot of, a lot of these trials are independent of us, meaning we just help them do the trial. But, so, a lot of them have been demonstrated now in the clinic, like diabetes type 2, and, you know, there are a number of papers, clinical papers on cancer. And so, most likely, the mechanisms are similar, right? So, we've shown in mice, we've shown in rats, and now we're seeing the effects on our human disease. Likely, it's the same mechanism, but we don't know, right? So, for example, the paper we just published on kidney damage in, in the rat, mouse and

• 41:35Valter Longo?

  rat, mice and rats, so very powerful, the FMD cycles in fixing the, the damage. But then in people, it was a small trial, but it was six patients and then seven patients in, it's called a randomized crossover trial, right? So, first six patients, and then we, we, a controlled diet, and then the controlled diet group goes into the FMD, right? And in both cases, remarkable effect on what's called proteinuria. So, the protein in the urine is evidence of, of kidney damage, right? So, and not only the proteinuria was, was reduced right after three fasting moving in the cycles in the kidney disease patients, but a year later, and the, the great majority

• 42:18Valter Longo?

  of them still maintained that benefit, right? And interestingly, when we look at this mesenchymal stem cells in the blood, kidney mesenchymal cells, so there are progenitor cells for, for kidney regeneration, they tripled in the blood of patients, right? So, we don't know, right? Is it? Are they being released to go to the kidneys? Are they being released in the bloodstream to go to the kidney and fix the problem? Or are they increasing the kidney and leaked in the blood? But it's really remarkable because you see a threefold increase in these progenitor

• 42:54Valter Longo?

  cells that are clearly mostly used to repair kidney damage or generate kidney tissue. So yeah, so in a lot of the trials, we see something very much consistent with what we see in the animal work. And of course, proving it is much more complicated. But in some cases, we may not need to prove it. So right now, do we need to prove, you know, the effect of the FMD and reversing diabetes? It'd be nice in humans, so we know how it works in mice. Do we need to prove the mechanism in humans? No, we just need to prove that it works, it is feasible.

• 43:38Valter Longo?

  And but yes, it would be nice eventually to show that, you know, for example, Harvard is interested in looking at pancreatic, in the type 2 patients, looking at whether beta cell regeneration process that we've shown in mice is also occurring in the patient, in the type 2 diabetes patients that are receiving fasting making dys cycles. So there are ways, I think, to look into is reprogramming stem cell based regeneration, et cetera, happening in people. It just takes a lot longer.

• 44:15Rich Roll?

  What is the receptivity in the traditional medical community amongst general practitioners or nutritionists and dieticians with respect to the work that you do? Fasting in general, the fasting mimicking diet? Because when you, you know, we could talk about longevity all day long and, you know, are we going to live to 120? But meanwhile, like, something like between 30 and 40% of Americans are suffering from type 2 diabetes or are prediabetic. Obesity rates are through the roof. Childhood obesity rates are through the roof. Heart disease is our number one. Like, this is what's killing people, right? And this is kind of where everybody should be focused in terms of.

• 44:58Rich Roll?

  Constructing a lifestyle to avoid these chronic lifestyle ailments. And your work and everything you talk about in your books, et cetera, seems to say pretty clearly and loudly like that this is a way out of that kind of death sentence that visits millions of people unnecessarily every year.

• 45:19Valter Longo?

  Yeah, and I think the two things are very much connected, right? So if you look at the major risk factors for diabetes, cancer, Alzheimer, and cardiovascular disease is aging, right? So if you just want to intervene on one thing, it's better to intervene on aging than intervene on obesity, right? So even obesity is dwarfed by the effects of 30 years of aging and any of these diseases, right? Meaning it's a very small effect. Of course, it's got a big effect. So, but it's very small compared to aging, at least 30 years of aging, right? So let's say that you could make people 30 years younger. That'd be the best way to go, right? Just make them younger and they can even be overweight, right?

• 46:04Valter Longo?

  But of course, the best way to go would be to do both, right? And this is what the fasting making, the longevity diet do. And by the way, unlike what we see with the GLP-1 agonist, so far, when we don't use drugs, we don't see lean body mass loss. It's very clear, trial after trial after trial, no lean body mass loss. We just don't see the bad thus far, right? Of course, yeah, you could say, when you have millions of people, maybe we'll start seeing some bad. But it's a very coordinated, it's very different, right? Than blocking an agonist, a GLP-1 receptor agonist. This is a very coordinated response.

• 46:46Valter Longo?

  And so there is not really a theoretical reason why there should be problems, right? And again, we don't see, in fact, in mice, we see bone density increase compared to the controls. So if you take mice middle age and we give them the FMD all lifelong, and we look at bone density, it's higher than in the controls, right? So that means that maybe there is even a bone regenerative, we don't know. I mean, I'm not claiming that there is, but there may be. But certainly in both mice and humans, we don't see muscle loss after even many cycles. And in fact, we did a trial with women with breast cancer, and even after many cycles of the FMD, if they had a good, healthy Mediterranean diet in between,

• 47:30Valter Longo?

  they actually increased limb body mass, right? The muscle absolute weight increased, and also the muscle function was increased. So this is, you know, by a what's called impedentiometry method. So we don't know, you know, that part, we don't know how carefully was measured. But certainly, in general, there seemed to be protection of muscle mass in these women, even after many cycles of the fasting making diet. So that's very important to get the reversed adiposity, so the fat storage, probably reduce the

• 48:10Valter Longo?

  inflammation. And we clearly see these anti-inflammatory effects of the fasting making diet. Go after the aging process. So for example, IGF-1 and all these aging markers are reduced, and they're reduced long term. You don't just see the insulin like factor one being reduced temporarily and then go back up. Laptin and IGF-1, they are reduced long term. And this is shown many trials, right? So yeah, so it's going after the adiposity, it's going after the aging acceleration or their aging rate, and it's doing so because

• 48:47Valter Longo?

  it's guided, right? And we developed a lot of this with that those problems in mind is not affecting the the healthy tissues, including bone and muscle.

• 49:01Rich Roll?

  Is there a use case for somebody who is severely obese to go on a GLP-1 and during that period of time, adopt the FMD until it becomes rote? Like it becomes like easy to do that? They're not, you know, kind of, they don't have the hunger pangs that they normally would have? And because, you know, your house is On fire, you gotta put the fire out before you can do anything else, right? Like to take a person through that for however many months and then wean them off of it and then kind of monitor their adherence on a longevity diet. Like, in your mind, is that, is that like a good way to go?

• 49:41Rich Roll?

  Like, if somebody is really like in a, you know, like a really acute unhealthy state?

• 49:48Valter Longo?

  Yeah, no, in my mind, that's option B, right? In my mind, option A, and I hope that, you know, eventually the government will also understand that we need professionals that are specialized in nutrition and they know what to do and they know how to do this carefully. And, you know, this probably involves molecular biologists, physicians and dieticians, right? That team, and maybe psychologists, right? None of this is reimbursed, or just the doctor part is reimbursed. But even the doctor part, it's not clear that it's reimbursed for giving nutritional and lifestyle advices, right? So I would say, you know, that would be the way this should be done.

• 50:28Valter Longo?

  The way we do it at the Curious Foundation is take your time, take a couple of years, and, you know, take the patient by the hand and say, okay, we're gonna get there. Don't worry about it. We'll, we'll address the hunger. We'll address all of it, right? It's a 360 approach and we'll get you there. There is no hurry. We'll get you there. In the absence of this, yes. So there is, for example, a physician in Dr. Bakarin in Brazil, who's been doing exactly what you just said, right? So she gives liraglutide, which is a short, it's a GLP-1 agonist that lasts than the new versions, right?

• 51:10Valter Longo?

  And, and so she combines the fasting making diet with the, with the liraglutide and then eventually she gets the patient off liraglutide and keeps them on the... And, yeah, so the hunger is, was her main problem. And she said, well, I just have an easier time with the patient by combining because then at some point, the, the patient say... Okay, I don't need the drug anymore. I'm good and I can see the effects of the FMD. And I'm just, then I continue with the FMD.

• 51:42Rich Roll?

  And the leucine glutathione is like a lower dose or less intense version of Ozempic or some other glutathione?

• 51:49Valter Longo?

  It's a shorter lasting Sunday that I think you have to give every day to the patient, right? So the health life is much shorter. It means that there is also less concerns because of course, these GLP-1 agonists are causing insulin production, right? And the fasting making diet cause insulin sensitization. So it means that it makes insulin work better. So now if you increase the insulin on one side and you make insulin work better, a lot better. And on the other side, you could have a problem because now you could get the blood sugar level very low, right? Very quickly. And so, yeah, that's why a continuous glucose monitor would be a very good idea. And a physician that really paying attention because for example,

• 52:31Valter Longo?

  we've done a trial on type 1 diabetes in children in Italy. This was the first use of the FMD in children. And we were very concerned about justice, right? Insulin injection and FMD. And the fact that maybe the nurses would not expect that the child all of a sudden with the same level of insulin would be much more responsive in controlling glucose. And so we saw problems, you know? Luckily, we were prepared. Everybody was wearing continuous glucose monitors. But we caught it on time, but we had some issues, even though I was very paranoid at the beginning. But they were not taking me very seriously. It's like, ah, don't worry about it. We do this all the time.

• 53:15Valter Longo?

  And but sure enough, we ended up in that situation, at least with one child. And so, yeah, so that was a very, very good to think of the worst, right? Think of the worst when you're combining drugs and fasting. This is why option A, I like it much more.

• 53:31Rich Roll?

  Yeah.

• 53:32Valter Longo?

  Because we don't see, you know, muscle loss. And it's also, I just wrote an article on this, is that You know, we are more and more underestimating the importance of the effort, right? So the effort of doing it like you did it, it's hard. I understand you cannot maybe do it on your own, but you got the professionals around you. They're helping you. Put the effort in and.

• 53:58Rich Roll?

  People don't want to hear that, Walter.

• 54:00Valter Longo?

  Yeah, no, I understand that, but but people have to hear that because, you know, I I wrote in the article, I talked about exercise and now in the 50s, nobody exercised. And then some, I forget the doctor came around and said, you know, people should exercise every day and people didn't know what that was. What is that? Why? And and I remember I read some of his interviews in the 60s and people were like, oh, people are gonna die if they're gonna exercise this much every day, right? And and then eventually the health of the world, you know, and hey, that's tough, right? That's much tougher than what I'm talking about to have to exercise regularly, right? So but people do it. So I I think that that's really the solution, also mentally, psychologically, you know,

• 54:43Valter Longo?

  in that article that I wrote, I said, you know, of course, you cannot tell everybody do 50 miles a week of exercise or running, right? Nobody's gonna do it. But, you know, if you make it reasonable, let's say 150 minutes, and that's what people do now, right? In in Europe and the United States, 150 minutes a week, a lot of people do it. It's it's not easy, but people manage and and I think it makes them happier, right? Then when they exercise, so.

• 55:11Rich Roll?

  Yeah, I think it's a broader conversation around our relationship with discomfort, right? And, you know, all good things are on the other side of the, you know, kind of uncomfortable things that you're avoiding, whether it's food, nutrition, exercise, or any other goal that you set for yourself. But the byproduct of of kind of grappling with that is well beyond like achieving the goal that you set for yourself because you've made this investment in yourself, you did the hard thing, you feel good about yourself, and suddenly you're more emotionally connected with your own well being and that spills over into like, not just your external outlook on the world in your own life, but like how you think about the decisions that you make,

• 55:54Rich Roll?

  food, exercise, et cetera, but, you know, the people you surround yourself with, everything. And all of that, you know, all of those things are fundamental to well being.

• 56:02Valter Longo?

  Yeah, but I agree with you. Let's say fifty, maybe sixty percent of the population is not going to accept that short term, right? I think for exercise, it took decades for the US and then the world, because this followed all over the world, right? It's, I think, an American idea. It took decades, maybe twenty or thirty years, to have a significant portion of the population actually saying, "I'm going to go jogging. I'm going to go and take a bike and do, you know, fifty K." So, yeah, so, so I think that, you know, before that happens, yes, we need to have methods that are, maybe including drugs for some, for a percentage, but certainly methods like, you know, the FMD.

• 56:46Valter Longo?

  And that's what I was saying earlier, we were testing it in Southern Italy, in one of the worst areas of the, either one of the worst or the worst in Europe, right?

• 56:54Rich Roll?

  Yeah, we think of Italy as sort of this, you know, giant blue zone, but it's not really that.

• 57:00Valter Longo?

  Not at all. I mean, if you look at Calabria and Campania. Yeah, so Calabria and Campania have surpassed the, the United States as far as overweight a portion in, in children, right? So it's a big, it's a big problem. And so the way we addressed that was, what about if we give an FMD for five days every three months? And everybody thought, "It's crazy, it's never going to work." We haven't published it yet, but let's say that it's looking good so far, right?

• 57:27Rich Roll?

  That's cool.

• 57:28Valter Longo?

  So, yeah, so now it gets down to very little, right? The five days every ninety days that you have to dedicate to this program in a box, essentially, a medicine in a box.

• 57:37Rich Roll?

  Yeah. Since we last spoke, I would say that there's been an explosion in interest in health span extension, longevity medicine, you know, this field in which you've invested your career and have been in for many, many years, a lot of energy right now. And everybody has their own kind of specific lane, whether it's AI, technology, in, you know, sort of the sophistication of scanning equipment, like all of these developments that are making health span extension, you know, more and more plausible. And I think, you know, among this group of people you share, there's many things, principles, ideas that you share in common, there are differences as well.

• 58:20Rich Roll?

  And I think one of the, the key ones with respect to diet is this emphasis on protein. So, somebody like You know, Peter Attia, Rhonda Patrick, they're always pushing protein, talking about the importance of protein, particularly, you know, after a certain age, certainly after age 65, when you really need to be eating more protein than you might think to maintain your muscle mass and, and you know, the kind of critical role that muscle mass plays in terms of how you're aging up. Your fasting mimicking diet and, and much of what you speak about kind of goes in the other direction. You know, maybe it's different when you reach

• 59:01Rich Roll?

  a certain age, but at least on the FMD, this is a pretty low protein protocol and it's not entirely vegan. It can be entirely vegan or, or pescatarian.

• 59:14Valter Longo?

  It's entirely vegan.

• 59:15Rich Roll?

  What's that entirely vegan? Right. I mean, you know, I've heard you talk about fish, you know, two or three times a week.

• 59:21Valter Longo?

  No, but it's every day diet, right?

• 59:22Rich Roll?

  Right, on the longevity diet, right. So maybe, you know, kind of state your case or your perspective on this controversial macronutrient.

• 59:29Valter Longo?

  Yeah. So first, let's take out the FMD, the fasting making diet, because it's just five days.

• 59:36Rich Roll?

  Sure, longevity diet, sorry.

• 59:37Valter Longo?

  Yeah, three times a year. And so it's completely irrelevant. So sometimes I've heard that argument that then maybe Peter made it, but I don't understand it because we're saying, you know, this is 15 days in a year. So even if you go zero protein, will have no effect whatsoever on your muscle, right? No effect. And we've shown this clinically in 10 different trials. In fact, in a new trial, we're actually showing increasing muscle mass after six cycles of the fasting making diet, right? And even not just relative, but absolute limb body mass, right? So that's clinically demonstrated to be false. If anybody's

• 1:00:18Valter Longo?

  saying the FMD is causing reduction of muscle mass, it's the opposite, right? So far, it's the opposite. The only time we see some limb body mass loss is in combination in the diabetes trials, in combination with drugs. That's the only time so far we've seen limb body mass loss. Then the longevity diet is very different. What about every day, right? So, yeah. So I think that. It is a big problem when we are using like a one or two pillar system to look at things, right? So you could, let's say epidemiology. A lot of people love to use epidemiology. Studies of big population, right? But, but even if you look at epidemiology, we've done that and we've done that. You know, in a, in a study published in JAMA with, with Harvard, we've done it on our own

• 1:01:03Valter Longo?

  study. It's pretty clear that you don't need a lot of proteins, right? And it's pretty clear from many, many studies that the people that do the best are mostly vegan, low but sufficient proteins. And then in our own paper, and we were the first one publishing on that, the 65 was the switch moment, right? So 65, we did not see, so people reporting a low protein diet, whether it was overall mortality or was cancer mortality, people that are reporting a low protein or very low protein diet did the best up to age 65 and then did not do so well after 65. So if an 80 year old said, "I have a very low protein diet," it did not do very well, either for cancer or for overall mortality.

• 1:01:48Valter Longo?

  So, and then the Harvard study with Giovanucci in the JAMA paper, I think that he showed, or we showed, because I was a co-author, that plant-based protein, high, high animal protein was not good, but high plant-based protein was associated with improvements, right? And that's where the devil in the detail comes in. Because there can be such a big difference, as I mentioned earlier, in amino acid levels in the plant-based proteins versus the, the animal-based protein, that it's not even clear what the meaning of protein is anymore.

• 1:02:30Valter Longo?

  Meaning that it's irrelevant because it's, it's really about 20 amino acids, right? So, so we should be talking about amino acid level and amino acid patterns. And that probably explains, so meaning that probably it's very clear that a low but sufficient amino acid intake is what you want up to a certain age. And by the way, the age should be biological age, it should not be chronological. So it could be 65 to somebody, but it could be 45 to somebody else and 72 to somebody else, right? So. At some point, and you see the population wait, instead of going up, it comes down, right? That's the point where we see this switch in immortality prediction.

• 1:03:14Valter Longo?

  Yeah, so then it's about amino acids. And again, epidemiology is one pillar, but then you have clinical studies, you have basic research. So how do you make a mouse live longer? Well, over and over and over and over for almost 50 years, low protein, low methionine diet, right? Just, you know, in rats, in mice, and no matter who did it. And so, yeah, so then that's like another pillar. And then the centenarians, whether you look at Okinawa, had a 9% protein diet, right? And for the longest time, had record longevity. So I will encourage my colleagues to, you know, just expand from one pillar science to, you know, five pillar, and the fifth is complex system.

• 1:03:58Valter Longo?

  But I say, even if you just go for four pillars, and if you go for four pillars, you see the devil is in the detail. It's about amino acids, and it's about having sufficient and protect the immune system, protect the muscle, protect the bones, but reduce as much as possible the aging rate. Because again, what dominates is aging. So that if you can make somebody younger, they will live longer, they will be much healthier. And again, there is a 10 to 30-fold difference between obesity and aging, and 30 years of aging as a risk factor for Alzheimer, cancer, cardiovascular disease, diabetes, etc., right? So, yeah, it's about aging.

• 1:04:39Valter Longo?

  The proteins are driving the growth factor, which are clearly at the center of the aging process in all organisms. And this is why our work with the Ecuadorians comes, come in, right? So the Ecuadorians have growth hormone receptor deficiency, and that's the protein pathway, right? So either mice, mice that have a growth hormone receptor or growth hormone deficiency are the ones that live the longest, live 40% longer with the lowest disease profile, right? This has been known, Jean Kupchuk, Andrei Barki, worked for decades. Now, surprisingly, in yeast, the 10-fold lifespan extension comes from the protein pathway, mostly from the protein pathway. So you block the protein pathway, and the yeast now are reprogrammed to live 10 times longer.

• 1:05:24Valter Longo?

  And then our work in Ecuador with people. Sure enough, people that have growth hormone receptor deficiency are protected, in spite of a terrible diet, are protected from diabetes, they're protected from cancer, they're protected from cognitive decline, they seem to have, and we brought them to LA to do a functional MRI test on their brain, they had the function of a much younger person cognitively, and now we just published on a neutral to positive effect on cardiovascular disease, which really surprised us, that the plaques were lower, or much lower, in the pathway, the response to protein intake is blocked, right?

• 1:06:06Valter Longo?

  The most damning part is the Harvard study showing a 40% increase in three different studies, in this, Frank Hou's work, three different studies, 40% increase in the diabetes risk in subjects eating high protein diet, right, compared to the lowest, I think it was quintile, so at lowest quintile versus the highest quintile, those that were in the highest quintile protein intake, in three different studies, almost identical results, right? So, yeah, so I think that it's really hard to imagine how, you know, how you could conclude from all of these studies, and we were talking about hundreds and hundreds of studies, that

• 1:06:50Valter Longo?

  a high protein diet is good for you. I mean, it should be sufficient, and was sufficient plus muscle training, right? That's very important. And a lot of studies indicate that the protein intake you need per mio is very low, it's around 30 grams per training session, right? If you have 30 grams of good quality protein with enough leucine, and that stimulates tor activation, you're gonna get maximized effects on muscle building, and that's probably, I mean, and you could do, say, even if you did it twice a day, you still be in a, you know, 60 grams, you still be in a relatively normal to low protein diet.

• 1:07:29Rich Roll?

  But beyond that is not to your benefit for reasons related to growth factor, I would presume that that would be offset for somebody who is extremely active, weight like, you know, regardless of age, if they're like in the gym and, you know, do, like, the negative implications of a higher protein diet would, would be abated by, you know, that very active person? Yeah?

• 1:07:55Valter Longo?

  Not necessarily, no. No, not necessarily, no. Because the growth factor, it could accelerate or is known to accelerate the aging process independently. So your active lifestyle could certainly help you in other ways live longer. But you're still, if you're accelerating your aging, your pro-aging pathways, that still can cause damage, right? That is still driving a faster aging rate in all your organs. Yeah, and then the exercise helps and maybe they could cancel out. But that's not what you want, right? You wanna maximize, reduce the aging rate and while, you know, increasing the functionality.

• 1:08:39Valter Longo?

  You know, so we are about to publish a couple of papers on that in MICE and but also in using the Harvard databases. And so, yeah, I cannot discuss it, but certainly it's very consistent what I'm saying, right? The data is that, you know, first of all, you need to really understand mechanism. How is each amino acid affecting which genes, which are affecting what processes? For example, we talk about stem cells and we talk about reprogramming. We see protein as the major blocker of the photos, right? Stem cell activation or self-renewal and reprogramming the Yamanaka factor, the reprogramming factor. It seems like if you wanna stop that process, high protein. And it makes sense, right?

• 1:09:23Rich Roll?

  And does it matter if it's animal versus plant?

• 1:09:25Valter Longo?

  Yes, because it's about amino acids. That's why I think eventually, I think very soon we should begin to move away from even using the word protein intake because it's completely irrelevant, right? Because if it was a 20, 30% difference between, let's say, legumes and red meat, you could say, okay, 23%. I mean, legumes and let's say soy, right? Or legume and seeds, seeds and nuts, right? So seeds and nuts, the amino acid profile between a seed protein and nut protein and a legume is huge, right? Then it's even bigger if you got red meat or even white meat, right? And sometimes it's up to 10-fold. So that's when it's irrelevant because...

• 1:10:11Valter Longo?

  You could have 100 grams of protein, which are providing 10% or 20% of that amino acid. And that amino acid may be the one that is making the big difference.

• 1:10:23Rich Roll?

  Yeah, I understand. And it's complicated. It's always more complicated than you think it's going to be, right?

• 1:10:27Valter Longo?

  Yeah. But it doesn't, it's not complicated in terms of are you implemented, right? So if you have a mostly plant-based diet, you just need to, and this is what I preach. Let's say that you're a vegan, then you should mix about a third, a third, a third plant. I mean, legumes, seeds and nuts, right? If you have that, then you're good to go, right? So practically, it's very simple, right? But if you only have legumes and you have already, so if you have a low protein intake and then it's all legumes, you're going to have a problem, right?

• 1:11:02Rich Roll?

  Because you're missing essential amino acids.

• 1:11:04Valter Longo?

  Yeah.

• 1:11:05Rich Roll?

  Because by focusing on one thing. Yeah, I mean, I think people, when I said complicated, I meant like, you know, this sort of physiological pathways and, you know, the science of it. I mean, the practicalities of it. As somebody who's been planting, I've been plant-based for a very long time. Like, people think that it's this complicated, time-consuming thing. But if you're just kind of grazing on a wide variety of plant foods, it really takes care of itself. Like, evolution has sort of, you know, figured it out. Like, I've just never really had a problem with this and have been confused by people who seem to kind of obsess on protein intake. Like, it's just, it's never really been an issue for me.

• 1:11:43Valter Longo?

  Right, right. But some people, let's say, you know, the Okinawa ones, you know, historically, and the Southern Italians, and maybe this is why they were so long-lived, right? But they were very frail. That's interesting, right? So if you look at Southern Italy, the same regions that have record longevity, because they used to have mostly legume diets, you know? Yeah, the seeds and the nuts were there, but not in the type of quantities that, so the legumes were very much available. And the rest of it was maybe less available. And not surprisingly, you see a frailty level that is almost twice as high as Central and Northern Europe.

• 1:12:23Valter Longo?

  So a lot of the Mediterranean countries are very frail, long-lived but frail. So I think that, you know, in your case, you probably had, you know, the muscle training and all of that and enough, you know, variety. But to a lot of people, you know, it could become a problem, right? So if you, you know, say five times a week, your proteins are all coming from legumes, then, you know, they might not be so easy to, if it's low protein and mostly from legumes, then it might be difficult to keep the muscle mass.

• 1:13:11Rich Roll?

  Are you familiar with this guy Brian Johnson?

• 1:13:14Valter Longo?

  Yes.

• 1:13:14Rich Roll?

  And his blueprint protocol?

• 1:13:17Valter Longo?

  Yeah.

• 1:13:17Rich Roll?

  You know, I gotta ask.

• 1:13:19Valter Longo?

  I mean, I don't know the blueprint protocol. I know the 100, you know, supplements and all that.

• 1:13:23Rich Roll?

  Lots of supplements, you know, basically, you know, putting a lot of time and resources and energy into, you know, trying to crack wide open this anti-aging equation. But part of it entails his diet, which is a entirely plant-based diet, limited to 2,000 to 250 calories, I think, something like that. It's very dialed in. His last meal of the day is at 11:00 a.m. So this is a fasting protocol. I think he goes to bed around 8:30 or 9:00 at night. He eats, you know, within, I don't know, 30 minutes of waking up in the morning, probably around 6:00 a.m. or something like that. And I think he has three meals throughout the day, small meals. Have you looked at this?

• 1:14:05Rich Roll?

  Do you have thoughts on kind of what he's doing here?

• 1:14:09Valter Longo?

  Yeah.

• 1:14:09Rich Roll?

  All his biomarkers seem to be fantastic.

• 1:14:11Valter Longo?

  Yeah, yeah. Well. Short-term effects may be completely irrelevant compared to the long-term effects. So a good example is, let's say, the breakfast keepers. The breakfast keepers, if you look at short-term, they may be actually very beneficial. And people argue that the breakfast keeper have a worse lifestyle and all that. But let's say that new clinical data suggests that it's not just that. It's not that. If you start eating later, you're going to have problems. But it may be difficult to see what's going to happen 20 years later. And you're going to get surprised. And the ketogenic diet could be another example.

• 1:14:56Valter Longo?

  So if you look at the ketogenic diet, very beneficial, very, it makes you impressive results. But in the long run, people on a low-carb diet, and there's lots of Harvard studies, they live shorter, or much shorter, much higher mortality, especially if it's low-carb, mostly animal-based diet. So yeah, so I would say that when you enter a lot of territories, the 100 supplements and eating within three-hour window, each one of them is a gamble, is a big gamble. And then if you put four or five together, now it's a very bad gamble. So you're exiting the territory of the five pillars in multiple ways.

• 1:15:41Valter Longo?

  So these centenarians eat in four hours, and no. Is there any data from mice? Yes, there is some data from mice that show that that's beneficial, or potentially eating within a smaller window is beneficial. So you have mixed data in lots of things that is doing, but a lot of it, I think, is going to be negative. So it's going to be, or not done before. So could it be positive? Yes. But it could also be negative or very negative. And so the surprise could come after 25 years, and it could be a big surprise. It could be a big surprise. And now that is causing a big problem. If people don't realize, you just need, like, for example...

• 1:16:26Valter Longo?

  Ketogenic diet. Well, everybody talks about the ketogenic diet and cancer as a positive thing. And it can be, right? And there's a lot of animal studies now, some clinical trials that are suggesting, and this is also in my book, that are suggesting that the ketogenic diet can be beneficial. But people don't talk about the cancers that are fed by ketone bodies, right? There's some cancers that grow much faster. And there's some cancers whose incidence goes up tenfold in people that have a high ketone body level, right? So, yeah, so then, very healthy short term, not so healthy for lifespan, and now associated with a much higher level of certain cancers, right? So this could be the surprise, right?

• 1:17:09Valter Longo?

  Now, all of a sudden, whatever you're doing, that is not, you know, within the domains of what's been tested for 100 years. And all you need is one of, let's say, 100 supplements, or even 10 supplements. People don't realize, I just looked it up the other day, and in Italy, drugs, just in Italy, drugs kill about 40,000 people every year. Drugs, right? Drug-drug interaction.

• 1:17:32Rich Roll?

  Not like recreational drugs you see?

• 1:17:34Valter Longo?

  No, no, no.

• 1:17:35Rich Roll?

  Prescribed drug?

• 1:17:36Valter Longo?

  Prescription drugs. Prescription drugs. It's 40,000 people a year. And in the US, it's a huge number. I don't remember. I just looked up the Italian number for some reason and not the US. But it's a huge number, right? So you combine lots of drugs, they start interacting in ways that you cannot predict. And so now, if you take 10 supplements, 20 supplements, 30 supplements, the higher the number, the more certainty, almost certainty, that it's going to cause a problem. It might take one year, five years, 10 years, but sooner or later, that's going to cause a problem.

• 1:18:09Rich Roll?

  For every additional supplement that you add into your routine, the complexity of how all of these things are interacting with each other, you know, kind of, you know, increases exponentially, basically, is what you're saying. And we don't know.

• 1:18:22Valter Longo?

  Even AI wouldn't be able to handle it for at least 20 or 30 years. They're so complex that you would need 20 or 30 years of data fed into AI to say, okay, this, now, the only AI understands that maybe...

• 1:18:39Valter Longo?

  That's going to cause a problem. But yeah, so, so right now, we're very far away being able to handle. Because you need big data, right?

• 1:18:46Rich Roll?

  Right. So how is the, you know, the selenium that you're taking interacting with the, you know, kind of the mega dosing of vitamin D, for example, or something like that?

• 1:18:56Valter Longo?

  Yeah. And because then the two are going to change the host metabolism or the host response. And now the new host response, so it's not just how the two interact, it's how the two change the body. And now the two plus the body change affect the third one that you're going to add, right? And or react. So all of a sudden, let's say your, your ferritin goes up, right? And now if you have a high ferritin and now you add some other supplement, now you have a recipe for disaster, maybe iron overload, because now you just have added the third supplement that is, is making the ferritin work less well, for example.

• 1:19:34Rich Roll?

  I see. You know, if you were counsel to Brian Johnson, you know, what would your, what would your advice be? I mean, I, I know I'm setting you up a little bit because you, you would have to know everything that he's doing, but kind of from a bird's eye view, general principle perspective.

• 1:19:50Valter Longo?

  Well, I mean, of course, I mean, the only thing that I will add to all the things that we discussed before, so time with the eating, the fasting making diet, the longevity diet, I will add personalization, right? So you, you will want to know everything about him and personalize all of it to, to him.

• 1:20:08Rich Roll?

  I think he would say that he, he probably has that dialed in. Like, I think he experimented with lots of different eating stuff with, with, with a big team of people who are weighing in and taking his blood markers like every day.

• 1:20:21Valter Longo?

  If that was the case, he wouldn't be eating in three or four hour window, right? I think he's underestimating the uncertainty of, of doing something that nobody's ever done before, right? If you just think about the short term effects, and this is the overestimation everybody's making, you have diagnostics and you think that because, you know, so I had big experts in the field telling me, you know, I have extremely low fat, you know, like 5% fat. Well, you know.

• 1:20:52Valter Longo?

  Data suggest that if you have a little bit higher fat levels, you may live longer, right? So, short term, you could say, you know, I have 5% fat, I'm gonna live forever. But the data is actually showing that those that live forever may be more in the BMI 25 range, right? Yeah, so then, that's this acute response and this idea that, you know, if you have a very low fat, that makes you very healthy, is misguided, right? Because that's not the case if you're trying to be, get to 110 healthy. And I don't mean just 110 frail, like the southern Italians, or maybe the Okinawan's, I mean 110 healthy. So then, you know, you have to have the five pillars, or more than the five pillars.

• 1:21:36Valter Longo?

  And those speak very, very clearly, right? And, yeah, so then on top of the five pillars, then you need the diagnostics, right? Then you need to say, okay, I'm using the five pillars. I came up with all these things, and now my cholesterol is still very high, right? Well, okay, that's not enough then. We need to intervene and make sure that cholesterol goes back to normal. And so, yeah, so I would say that, again, if you look at the longevity records, it comes from mutations that do lots of weird things, like growth hormone receptor knockout, right? It make mice and people very short, right? So, it's very counterintuitive, let's say, because a lot of people inject themselves with testosterone or growth hormone to live longer, and yet, clearly, after 100 years of research,

• 1:22:21Valter Longo?

  high growth hormone is making mice and probably people live the shortest, yeah.

• 1:22:28Rich Roll?

  Right. Speaking of people who are short, I came across that CNN article about Laren syndrome, and people who are genetically very small, like four feet and under, who really don't get lifestyle disease, or cancer, or heart disease as readily as we do. And I know you've done some work with this. Community, right?

• 1:22:51Valter Longo?

  Yeah, so this is what I was just talking about, right? So the growth hormone, the little people that you're referring to have a mutation in the growth hormone receptor, right? So this is why I was saying, people are now a lot, millions of people around the world are using growth hormone injections to become younger, right? And so if you look at them short term, you probably conclude that they are younger or they're functioning better, let's say, right? And so, but the mouse and the human data suggest exactly the opposite, right? So the little people, it's like if you inject them with growth hormone, they'll have absolutely no effect, right?

• 1:23:30Rich Roll?

  The receptors don't.

• 1:23:32Valter Longo?

  They're missing the receptor. You have the key, but you don't have the keyhole. So worthless key, right? And so those mice and people that have the blockade in the growth hormone pathway are the one that by far are doing the best, right? By far. I mean, if you look at, you know, mice, there is nothing that even comes close to this growth hormone and growth hormone receptor. And that's nice because it can be that the mice are lacking growth hormone or lacking the growth hormone receptor. Either way, they have record longevity and record health. And this has been shown, you know, we work with these mice, but lots of laboratories. So there's really no doubt about it, right? So, yeah, so that's why this genetics data is so important

• 1:24:17Valter Longo?

  and it's part of the, you know, I put it in the centenarian, you know, the people that have lived with that change for 100 years, right? So now we have the data both for the Laron's, but also for the Okinawans and for the centenarians of Southern Italy or La Malinda.

• 1:24:36Rich Roll?

  So your research and your latest book, Fasting Cancer, appear to support

• 1:24:43Rich Roll?

  The thesis that the fasting mimicking diet, in conjunction with traditional treatments for cancer, seem to have a beneficial impact in terms of recovery and remission rates. In general, right? Within the context of a very complicated field.

• 1:25:05Valter Longo?

  I mean, differently from diabetes. Cancer is really 100 different diseases, maybe 1,000 different treatments. So I would say that in general, especially for those that have advanced-stage cancer, say, stage 3, stage 4, the ones that are in trouble. Lots of the clinical studies are now showing that it seems to have a big effect, right? Making the whatever, especially chemotherapy thus far, better, right? So one of the nicest ones that I mention in the book is that triple-negative breast cancer, very aggressive. Women with metastatic cancer, the fasting-mimicking diet now is nearly doubling

• 1:25:48Valter Longo?

  overall survival in the first study by Vernieri and colleagues. And then they just published a follow-up paper, which is not in the book, showing either chemotherapy alone, chemotherapy plus fasting-mimicking diet, or chemotherapy plus fasting-mimicking diet plus Metformin. And again, nearly a doubling compared to the the expected survival of what's called PCR, complete pathological response. These are just a few trials, but there's lots of them that are indicating that the fasting-mimicking diet is, you know, making survival better, making also the pathological response better, right? So if you look at the masses,

• 1:26:31Valter Longo?

  the cancer masses after the treatment, they seem to have less active cancer cells. Now, you know, there's also an argument, and this is why we say be careful. As I mentioned earlier, like, you know, if you misuse it, let's say, you say, oh, fasting, all fasting is good, and so I'm going to get chemo, and then I'm going to re-feed at the same time. That could cause problems and not solution. And the other thing is, you know, fasting-mimicking diet has a very powerful effect on stem cells.

• 1:27:02Valter Longo?

  And so, you know, we've looked at cancer stem cells and we've shown that in breast cancer it reduces cancer stem cells. But others have indicated that in some cases it could increase cancer stem cells, right? So in the early stages of the disease, right? So we don't know enough about it. We really haven't seen that. But I would say if it's early stage and the treatment is likely to be very effective, stick with just the treatment and don't try anything else. Maybe the longevity diet, maybe the 12-hour timer instead of eating. And this is what we do in the clinics. We say it's early stage and you have a 98% chance of being cured by it, just leave it alone.

• 1:27:47Valter Longo?

  Now, you know, it could be that it will have helped you a lot, even in these early stages, but it could be that there's something that we don't know yet. And so I know people think we're paranoid, but I think it's a good way to look at it. And unfortunately, a lot of people don't look at it that way.

• 1:28:03Rich Roll?

  So essentially, it's going to be case-dependent, depending upon what type of cancer and how advanced that cancer is. More advanced cancers and certain types of cancers seem to indicate that traditional therapy, i.e. chemotherapy, in conjunction with a fasting-mimicking diet, seems to have a beneficial effect that outweighs chemotherapy alone.

• 1:28:33Valter Longo?

  Well, I mean, if you look at the animal studies, right, then it's just overwhelming with all kinds of cancer, you know, colorectal, lung, and breast, and name it, right? Then fasting-mimicking diet plus chemo, immunotherapy, hormone therapy, kinase inhibitor, I mean, just phenomenal effects, right? And I mean, turning cancers that are clearly... So we published a paper a few years ago, showing hormone therapy, for example, right? Hormone therapy, so palbociclib fulvestan, this is in mice, right? And we also had the clinical trial, but in mice is very conclusive. You use the standard of care, palbociclib and fulvestrant.

• 1:29:16Valter Longo?

  And the tumor is kept in check, just like it is in people for a while. And then it starts adapting and it starts growing, right? You had the fasting making diet cycles. And now you see the tumor going the opposite direction until it goes to zero. So it's just over and over and over. The animal data is remarkable and really almost surprisingly, and it's not just my data. It's now a lot of labs that are looking at it. It's just remarkable. For example, in mice, we published two papers and some Spanish groups have done the same. Immunotherapy in mice does almost in some of these models for like say breast cancer and even melanoma, that's very little. And the fasting making diet alone does more than immunotherapy, right?

• 1:29:57Valter Longo?

  So I would say the potential is huge in all the different cancers and in all the different stages. But because there is a system and the system should be respected and we don't know yet. We haven't tested it for a lot of clinically, we haven't tested it. In mice, we tested it, but not clinically. You know, that needs to be done before somebody. And this is why my comment about definitely if you're stage four and nothing else is working.

• 1:30:26Rich Roll?

  Yes.

• 1:30:27Valter Longo?

  Go for it, right? Because the animal data is phenomenal. But if you're stage one and you already know that what's been done for 20 years is working very well, then I don't think you want to take a chance, right? Stick with the standard of care and then God forbid you get to the next level, then yes, then consider it.

• 1:30:50Rich Roll?

  Yeah, I think that you're very, you know, kind of circumspect in the way that you you talk about, in the way that you just did, you know, throughout the book, like, hey, listen, I'm not like here to tell you like this is some panacea, right? Like, here's what we're seeing right now. Here's what I'd like to see. Here's some research that still needs to get done. I'm not telling you to not, you know, pursue every traditional therapeutic modality there is. I'm just saying, you know, in my lab and in other people's research, this is what we're seeing right now. There's something interesting happening here. I think it's worth pursuing and investigating, you know, more thoroughly.

• 1:31:26Valter Longo?

  Right, right. But in some cases, the clinical trial, like for triple negative breast cancer, and even for hormone therapy, I mean, for triple negative breast cancer, you're starting to see randomized trials showing a big difference, right, from what you expect or from what the control arm has, right? So, and this is in patients. So, yeah, for those, I would say, probably talk to your oncologist and say, hey, what about these three or four papers, you know, it's looking good.

• 1:31:57Rich Roll?

  And how up to speed are the oncologists, you know, in this, in this field?

• 1:32:01Valter Longo?

  Some are up to speed and a lot of them are not, right? So, and a lot of them are gonna wait for an FDA approval, which, you know, may or may not come, right? So, this, some of these, it's very expensive, you know, hundreds of millions of dollars to get an FDA approval. The FDA looks at fasting making diet, it's very complicated. So, we talk to the FDA to make it feasible or to make it appropriate for the FDA. You probably need to, you know, take the 60 ingredients or so in the fasting making diet and make it into six or seven, which will make it very difficult to do and very difficult for the patient, right? So, you know, it may or may not end up in FDA approval. And so, I think the way

• 1:32:45Valter Longo?

  to go is for the oncologist to be informed and to follow. And there's gonna be a point where there's gonna be enough trials that, and there is enough standardization of the diet that the oncologist could say, hey, this has been tested in, you know, seven or eight trials. It's very, it looks very good and I'm gonna recommend it.

• 1:33:04Rich Roll?

  Is breast cancer the form of cancer in which you're seeing the most kind of optimistic, positive indications?

• 1:33:11Valter Longo?

  No, not in the animal studies, it's working very well with all kinds of cancers.

• 1:33:16Rich Roll?

  In humans, though?

• 1:33:17Valter Longo?

  Yeah. In humans, is breast cancer just being tested a lot more? It's not that we tested the others and it didn't work. It's more that-

• 1:33:26Rich Roll?

  We know this disease better.

• 1:33:27Valter Longo?

  Well, there is more effort dedicated clinically to breast cancer. So, you know, for whatever number of reasons, but there's more studies, more clinicians come to us and say, I would like to do a trial on, you know, hormone therapy. And breast cancer or chemotherapy in breast cancer or immunotherapy in breast cancer. But now that we're starting, you know, they're starting our trials on colorectal cancer. We finished one on prostate cancer. Eventually, hopefully, we'll, we'll have a lot more. But yeah, there just hasn't been in that many trials in any other cancer other than breast cancer.

• 1:34:11Rich Roll?

  There's one randomized study that you talk about in the book with respect to breast cancer. 131 patients showed very promising results in the context of the fasting mimicking diet being kind of woven into their, their treatment protocol. 90 to 100% tumor free masses were seen in only 8% of patients who completed chemotherapy without any FMD, 29% with one cycle of the fasting mimicking diet, 33% with three or four cycles, and 53% with all chemotherapy cycles combined with a fasting mimicking diet. I mean, that 131 patients,

• 1:34:55Rich Roll?

  not the biggest population, but not insignificant either. Like, that's, that's a considerable result.

• 1:35:04Valter Longo?

  Yeah. Yeah. And this is being confirmed by the Vernieri paper that we just published very recently in cell metabolism. But I think that I like, I'm a little worried, you know, that that's too early because that trial was in women that were to receive the surgery. So early stage about to receive surgery. So I think that, you know, we'll see, but it falls into the category of too early to try it until there's more clinical data, right? But whereas in the metastatic setting, where we're seeing the same exact results with,

• 1:35:47Valter Longo?

  with the, very similar to what you just described, but now in patients that are, have metastatic cancer. Yeah, then I think that that's a very different scenario. It's working very well, and that's where we've seen the overall survival difference, at least in the early trials. So I'm more optimistic and excited about the metastatic one than the early one, because the early one in that trial is not enough to make conclusions about long-term survival. And so, and it's very, very early before surgery. So, yeah, I don't know. I don't want to make that category of breast cancer patients too excited about,

• 1:36:29Valter Longo?

  you know, oh, I'll do this, because, again, I'm worried about the cancer stem cells and other things that could be affected in different ways. Now, yeah, I don't have that worry for the metastatic, because, again, it's been tested now more, and we see no evidence of, and we see the overall survival improvement. And so, yeah, so I think that definitely a wild card, I will call it that, a wild card for any cancer patients, you know, of course, after a discussion with the oncologist, for any cancer patient that is in the situation where this is not working, right? And then the oncologist says, you know, doesn't look good.

• 1:37:14Rich Roll?

  That's it, you know, two to six months, and there's not much more.

• 1:37:18Valter Longo?

  And not just that, it could be stage four, you know, three to four years, but it's not working very well, and we're concerned, right? So, yeah, that's the, if the oncologist comes back with, okay, this didn't work, but we have this, and this could work extremely well, right? And we're very confident, okay, then try that. But at the point where the oncologist comes back and say, there's really nothing left. And, yeah, you could still live seven or eight years, but we just don't have anything right now. That's when I would, I would definitely talk to them, and this is what the clinic, the foundation clinics do, are working with the oncologists and saying, okay, this is a good time to give it a shot, right? So, and see what happens.

• 1:38:01Valter Longo?

  Hey, and the book is full of stories, and this is why I make sure that I don't make the stories into a reality. And there's people that, like, you know, Vernieri published five cases. Of, you know, stage four colorectal lung cancer. And in fact, the lung cancer patient that

• 1:38:21Rich Roll?

  Yeah, Maggie Jones. I mean, that was like the most impactful story in the book, I thought.

• 1:38:26Valter Longo?

  No, Maggie, yeah, but then in the Vernieri, I didn't talk about it a lot, but in the Vernieri study that is published in European, I think, cancer journal. There is five cases and one of them is lung cancer and the person was a friend of the oncologist, right? A good friend of the oncologist. And, you know, the oncologist thought, yeah, there's nothing we can do, you know, lung cancer, stage four. The person went into remission, which shocked so much all the oncologists at the Italian National Cancer Institute that they published a paper on this because they say, we never seen five patients out of a single trial with stage four going to remission, right? And so, yeah, so they were so surprised that they decided to publish a paper saying,

• 1:39:09Valter Longo?

  okay, we don't know, it could be a crazy coincidence, but that's a little strange, right? That we're seeing all this, essentially, you know, I don't know if I want to call it that sentence, but certainly, you know, there is not much hope left, right? And then, you know, seeing, in one case, I think it was the colorectal, the cancer came back after three or four years, but there was already, and then the same treatment and the same result. So, yeah, so I think the hope that there is something that could make a big difference, right? That's, that's the thing what we got right now. And, you know, hopefully we'll have the demonstration of it in big clinical trials.

• 1:39:49Rich Roll?

  From a mechanistic point of view, the way you describe it in the most basic sort of layperson manner in order that, you know, normal people can kind of understand what you're getting at is that you use this analogy of cancer cells as these sort of food stealing thieves, right? The FMD is sort of an attempt to starve them, in other words, like close the grocery stores, right? That at the same time, don't impact normal healthy cells in the same way they impact cancer cells. And through autophagy, like they can kind of, you know, kind of regenerate themselves, regenerate healthy cells. Is that, is that?

• 1:40:29Valter Longo?

  Yeah, I think the normal cells have been trained for 3 billion years, right? So they know exactly what to do. Bacteria, if you starve them, they know exactly what to do. Yeast and all organisms on Earth. Most organisms on Earth, by the way, are in starvation, are starving right now, right? If you look at microorganisms. So the normal cells, they know exactly what to do. The cancer cells have evolved with excess food, right? They only understand a lot of food and they don't understand how to make their own food. They understand that, "Yeah, I gotta get it from the bloodstream," right? So if you just do fasting or fasting-making diet, they're not happy, you know? But this, we see over and over, kind of like a cycle of chemotherapy. It's about the equivalent.

• 1:41:13Valter Longo?

  So if you just do fasting-making diet cycles, they love the slowing down effect of cycles of chemotherapy. But then, when you combine it with chemo and we combine it then with immunotherapy, when you combine it with hormone therapy, et cetera, et cetera, that's where you see, you know, in a lot of cases, we actually can drive the cancer down to zero or, you know, really stop it, you know, stop its growth for a very, very long, for a very long time. So, so I think, yeah, the cancer cells are confused. And now we have this technology that I talk about in the book, which is, we call it "starvation escape pathways," blockade, right? So, so basically, we use technology to say, "Okay, I starve the system with the fasting-making diet.

• 1:41:57Valter Longo?

  But then I take the cancer cells and I look at how they rewire using this RNA sick technology, right? So I can show, I can see very rapidly and potentially now even using cells from the blood that I just collect. And so hopefully, soon we'll do that in people. So I can see how they rewired and I can use drugs that are available to block that particular highway, right? So I know what the highway you're gonna take, basically, and I just block it, right? And that's really, we publish this incredible effect, right? So alone, does, yeah, delays it a little bit. Then we identify the escape pathways and we block it

• 1:42:38Valter Longo?

  and tumor comes down and stays down, you know, either for a long time or permanently.

• 1:42:45Rich Roll?

  So what is the message that you're trying to convey in this book? Because there is a sort of caution, like, okay, don't get too excited. You know, I'm talking about a very, you know, specific set of circumstances in which, you know, kind of what I understand would apply. So, so, you know, who's the, who's the reader for this? And what is it that you want people to kind of get from it?

• 1:43:06Valter Longo?

  Yeah, well, first of all, everybody in the cancer prevention setting, right? So treat aging, prevent cancer, and that could have a remarkable, you know, whether it's a fasting making diet, or the longevity diet, or the time restricted eating, or the, you know, other things that are in there. So prevent cancer. Then if you're unlucky enough and you get cancer, you know, at the beginning, you can still do lots of things like longevity diet, time restricted eating, different, right? So now time restricted eating, we go to 14 hours from 12. If you are a cancer patient, right? So we increase it to 14 hours. And longevity diet, we have to work on, you know, making sure that you don't lose muscle, your immune system doesn't get weaker.

• 1:43:50Valter Longo?

  And so that's an everyday diet. Then the fasting making diet is only, I think, for patients that need to do it, right? So if you're early stage and everything is, you know, you're having low levels of side effects and everything is smooth, I would say just do the longevity diet and time restricted eating and do lots of other things that we talk about in the book. But that's it, you know? If you are metastatic or the oncologist says, nothing is working here, even though you're not metastatic, yes, then I think I will consider the fasting making diet and then I will talk to the oncologist and see what he or she has to say about using it.

• 1:44:35Rich Roll?

  What is your sense of the impact that AI is having or will soon have on your specific field of study?

• 1:44:43Valter Longo?

  Yeah, I mean, what I just said, I think eventually AI will make that process of identifying the escape pathways and the drugs very quickly, almost immediate, right? And I'm not talking about 20 years, I'm talking about two or three years. So in two or three years, I think we could probably, if we had enough money, now if the NIH is shut down, maybe we won't. But I think in two or three years of enough funding, we'll be able to use AI to very quickly get to the escape pathways, you know? And so the idea would be, I use the FMD as a wild card, and I use the AI to tell me what the other drugs are, and then I use FDA, already FDA approved drugs to block it, right? And so it's a little bit of a science fiction world, you know, I call them cancer antibiotics, right?

• 1:45:28Valter Longo?

  So, yeah, so I see that with enough funding, you know, in the next 10 years, we might have this sophistication to say, you know, kind of like antibiotic, you go to the doctor and say, oh, you know, you have an infection, so we'll give you this antibiotic, let's see if it works. So I think, you know, and maybe I'm optimistic with the time, but I think, you know, with the right funding, this could happen in the next 10 years where, you know, you get your cancer antibiotics, very low toxicity, kind of like FMD++ plus, very low toxicity drugs that you can just take, and let's see if the cancer goes away. And, you know, if it doesn't go away, then we'll try something else. But, yeah, I think that's clearly theoretically, but also using the animal data, this is very close, right?

• 1:46:13Valter Longo?

  But, yeah, so sometimes it could be very close, three years, it could be very close, 30 years, you know, it's hard to know, but I think, you know, with the right funding, it could be within 10 years.

• 1:46:25Rich Roll?

  And outside of the cancer context, are you among the techno optimists in terms of how AI is going to impact health span extension in, you know, a wide variety of ways, you know, kind of beyond your area of expertise specifically?

• 1:46:41Valter Longo?

  Yeah, I'm very scared the way I so I don't like it at all.

• 1:46:45Rich Roll?

  Well, here's sorry to interrupt, but I just say one thing I've said this before on the podcast, but like, you know, I've had, you've all know a Harari on the podcast and he's, you know, sounding the alarm about like, you know, the sort of end of democratic systems and humanity at large. But we were both at the Google Zeitgeist conference and it's just, you know, Pollyanna all day long in terms of like, how amazing it's going to be.

• 1:47:08Valter Longo?

  Yeah, yeah, very scary, right? Very scary. Yeah, I, you know, I think to see how scary it is, you have to look at evolution, right? Systems evolve, right? And, and it doesn't really matter whether that system happens to be, you know, a derived from single cells or from a programmer. That's the scary part that I think everybody is underestimating. You know, if, if, if every system can evolve, it can find its way, right? And, and so that's a scary part. And now for the first time ever, we have a system that evolves and is based on,

• 1:47:48Valter Longo?

  you know, a program and it can learn and, and, and eventually, you know, where can it end up, right? So that's, that's what sets the stage for, it's just a matter of time before it's going to evolve, right? And it's going to find its way and the question is, what way is it going to find? Well, if you look at the past, right, then, and, and dinosaurs and all kinds of organisms,

• 1:48:13Valter Longo?

  you know, you, you could see that, you know, some of the evolution could end up in the, in the wrong place for, for humanity, right? And, and as a, as a antagonist. So yeah, that's what I'm worried about. Of course, I agree with all the benefits, you know, I just talked about one. But, but it's not something that we couldn't do computationally anyways, right? So, so I think that. I mean, I don't know, maybe there's, there is nothing we can do, right? We cannot block AI. So, so I think we could regulate, right? And, and begin regulated, you know, in a, in a planet wide manner. And so that's probably the thing that we need to do very quickly.

• 1:48:54Valter Longo?

  That, that would be my, my suggestion as somebody that, that, you know, works on evolutionary biology. We need to use its power, but also, um, understand its power and regulate it as soon as possible. And I don't really see any, any, because everybody's thinking about making money using it, right? This is really entertaining, right? That, that, um, you know, imagine generating a dinosaur and thinking about how much money you're gonna make in Jurassic Park, right?

• 1:49:24Rich Roll?

  Well, this is happening. The woolly mammoth is underway. That company just raised like some crazy amount of money and like it's gonna, that's what, that is what is happening.

• 1:49:34Valter Longo?

  Yep, yep, we have more problems than AI than I guess. But yeah, so I think that we, I don't understand. I mean, maybe it's just the obsession with making money that is driving this irrational exuberance that has very little worst case scenarios, right? You know, what's the worst case scenario? Well, if the worst case scenario is really bad for, for human beings, then probably not a good idea to, to not regulate it, right? So.

• 1:50:07Rich Roll?

  We talk about regulating it, but not really, you know? I mean, I think there are a lot of smart people who are, who are thinking deeply about this, but the momentum behind this just moving forward is too great at this point. And I think, yes, like money is central to the whole thing, but I think beyond that, it sort of just speaks to the ingrained nature of the human animal. Like, you know, we're nothing if not a creature that is just gonna keep doing the thing and will like deal with the circumstances in the aftermath. And yeah, we'll give lip service, we could, we better be careful, but. We're bowling forward no matter what. And that's what I see happening. And I think in the short term, like certainly,

• 1:50:52Rich Roll?

  there's incredible implications that, you know, for this that are going to benefit humankind specifically in, in, you know, the healthcare context. I think these tools are going to be remarkable in terms of identifying diseases at the earliest stages and figuring out ways to circumvent them and cure them and prevent them. All of that, I think, you know, is something to celebrate. But there is the kind of larger looming existential questions that are a little bit, you know, harder to kind of grapple with and determine solutions. But I think we lack the adequate humility to really respect the gravity of what we're doing. And I think we think we might know what the implications are, but I don't think we really do at all.

• 1:51:37Valter Longo?

  Yeah, and I mean, if you look at nuclear power, right? So some of the same arguments were made. And right now, we're in a situation that we probably rather not be in, right? Somebody goes crazy, it just wipes out the entire planet. So this is much worse, right? I mean, compared to the AI, I think the danger of nuclear power is very small, right? That's why it's particularly surprising that we don't see it for how powerful it can be. And it will be. I mean, it's not a can be, it will be. What happens then, right? So I don't know if we went back and, you know, in the, in the nuclear science, we had made the same choices,

• 1:52:21Valter Longo?

  if we had a choice at some point back in the past, right? I mean, I don't know right now that, you know, everybody would like to be in a world where everything could be wiped out by just an event that goes in the wrong direction, right? So, yeah, so there's a lot of benefits, but maybe, maybe it wasn't worth having those benefits available to us. Considering where we are right now. Yeah, so in AI, I think it takes it to another level.

• 1:52:54Rich Roll?

  Well, we're going to find out. And since you're on a track to living between 120 and 130 years, hopefully, we have it figured out so that you can live a long and fruitful life. And you're going to have a baby soon, yeah?

• 1:53:07Valter Longo?

  Yeah.

• 1:53:08Rich Roll?

  So you're probably thinking about things more philosophically.

• 1:53:11Valter Longo?

  Yeah, that's what makes me worry, right? So, yeah.

• 1:53:14Rich Roll?

  Yeah. Well, I appreciate the work that you do. It's a service to humanity. And I just want to acknowledge you for that service and appreciate you coming here and sharing with us. And you're always welcome here. The new book is Fasting Cancer. And if people want to learn more about your work specifically, Walter, where should they go in addition to checking out your book?

• 1:53:36Valter Longo?

  Instagram, I think Professor Walter Longo on Instagram and also the Creative Cures Foundation. That's, you know, createcures.org, I think.

• 1:53:47Rich Roll?

  Yeah, excellent.

• 1:53:48Valter Longo?

  Thanks a lot, Rich. Great talking to you.

• 1:53:50Rich Roll?

  Cheers.

• 1:53:50Valter Longo?

  Peace.

• 1:54:10Rich Roll?

  That's it for today. Thank you for listening. I truly hope you enjoyed the conversation. To learn more about today's guest, including links and resources related to everything discussed today, visit the episode page at richroll.com where you can find the entire podcast archive, my books, Finding Ultra, Voicing Change, and The Plant Power Way, as well as the Plant Power Meal Planner at meals.richroll.com. If you'd like to support the podcast, the easiest and most impactful thing you can do is to subscribe to the show on Apple Podcasts, on Spotify, and on YouTube, and leave a review and/or comment. This show just wouldn't be possible without the help of our amazing sponsors,

• 1:54:53Rich Roll?

  who keep this podcast running wild and free. To check out all their amazing offers, head to richroll.com/sponsors. And sharing the show or your favorite episode with friends or on social media is of course, awesome and very helpful. And finally, for podcast updates, special offers on books, the meal planner, and other subjects, please subscribe to our newsletter, which you can find on the footer of any page at richroll.com. Today's show was produced and engineered by Jason Camiolo. The video edition of the podcast was created by Blake Curtis, with assistance by our creative director, Dan Drake. Portraits by Davy Greenberg. Graphic and social media assets courtesy of Daniel

• 1:55:35Rich Roll?

  Solis. And thank you Georgia Whaley for copywriting and website management. And of course, our theme music was created by Tyler Piotte, Trapper Piotte, and Harry Mathis. Appreciate the love, love the support. See you back here soon. Peace. Thanks.

• 1:55:51Valter Longo?

  Namaste.